Submissions for variant NM_012210.4(TRIM32):c.811C>T (p.Arg271Trp)

dbSNP: rs372298402

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000425132	SCV000514967	uncertain significance	not provided	2019-09-27	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Illumina Laboratory Services, Illumina	RCV001253942	SCV001429824	uncertain significance	Sarcotubular myopathy	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001254018	SCV001429916	uncertain significance	Bardet-Biedl syndrome 11	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001309593	SCV001499098	uncertain significance	Bardet-Biedl syndrome	2022-08-23	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 271 of the TRIM32 protein (p.Arg271Trp). This variant is present in population databases (rs372298402, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TRIM32-related conditions. ClinVar contains an entry for this variant (Variation ID: 378760). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002524809	SCV003716722	uncertain significance	Inborn genetic diseases	2021-10-06	criteria provided, single submitter	clinical testing	The c.811C>T (p.R271W) alteration is located in exon 2 (coding exon 1) of the TRIM32 gene. This alteration results from a C to T substitution at nucleotide position 811, causing the arginine (R) at amino acid position 271 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000425132	SCV004160652	uncertain significance	not provided	2023-01-01	criteria provided, single submitter	clinical testing	TRIM32: PM2
Fulgent Genetics, Fulgent Genetics	RCV005044634	SCV005682484	uncertain significance	Sarcotubular myopathy; Bardet-Biedl syndrome 11	2024-01-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003942332	SCV004765963	uncertain significance	TRIM32-related disorder	2023-11-21	no assertion criteria provided	clinical testing	The TRIM32 c.811C>T variant is predicted to result in the amino acid substitution p.Arg271Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.042% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.