Submissions for variant NM_001101426.4(CRPPA):c.79A>C (p.Thr27Pro)

gnomAD frequency: 0.00220  dbSNP: rs558064127

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000173205	SCV000224300	benign	not specified	2016-08-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000292121	SCV000468024	uncertain significance	Congenital Muscular Dystrophy, alpha-dystroglycan related	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001721100	SCV000490568	likely benign	not provided	2020-06-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29382405)
Invitae	RCV000531834	SCV000652589	uncertain significance	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7; Autosomal recessive limb-girdle muscular dystrophy type 2U	2022-10-18	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 27 of the ISPD protein (p.Thr27Pro). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with muscular dystophy (PMID: 29382405). ClinVar contains an entry for this variant (Variation ID: 193158). 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.
Athena Diagnostics Inc	RCV000173205	SCV001880129	likely benign	not specified	2020-11-10	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001721100	SCV003828641	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927580	SCV004752475	likely benign	CRPPA-related condition	2019-07-17	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).