Submissions for variant NM_001378454.1(ALMS1):c.4228G>C (p.Ala1410Pro)

gnomAD frequency: 0.00025  dbSNP: rs201517720

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000634777	SCV000756120	uncertain significance	Alstrom syndrome	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1411 of the ALMS1 protein (p.Ala1411Pro). This variant is present in population databases (rs201517720, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 529369). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx	RCV001702699	SCV002038960	uncertain significance	not provided	2024-05-16	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genetic Services Laboratory, University of Chicago	RCV001701140	SCV002070954	uncertain significance	not specified	2019-01-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002331133	SCV002630446	uncertain significance	Cardiovascular phenotype	2023-05-11	criteria provided, single submitter	clinical testing	The p.A1411P variant (also known as c.4231G>C), located in coding exon 8 of the ALMS1 gene, results from a G to C substitution at nucleotide position 4231. The alanine at codon 1411 is replaced by proline, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV000634777	SCV002780990	uncertain significance	Alstrom syndrome	2022-02-18	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000634777	SCV001463042	uncertain significance	Alstrom syndrome	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001701140	SCV001921422	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702699	SCV001927377	likely benign	not provided		no assertion criteria provided	clinical testing